Transposable Elements Teach T Cells New Tricks Comment

Mammalian genomes are replete with transposable elements (TEs): parasitic genetic sequences that can replicate to high copy numbers within host genomes (1). TEs are widely recognized as a potent source of cell type- and context-specific regulatory elements (2, 3). In PNAS, Ye et al. (4) analyze chromatin profiling data from mouse CD8+ T lymphocytes and find that multiple TE families contribute to predicted regulatory sequences. Compared to other cells, immune cells show the highest enrichment of TE-derived enhancers (Fig. 1), suggesting that TE cooption may preferentially influence immune regulatory networks. Fig. 1. Ye et al. (4) observe higher occurrences of TEs near immune genes. They hypothesize that the abundance of TEs in immune-associated regions of the mouse genome has enabled their regulatory cooption as immune enhancers, potentially facilitating the rapid regulatory evolution needed for adaptive immunity. Transcriptional regulatory networks underlie the gene expression programs that determine cellular identity, function, and response to stimuli. In the genome, regulatory elements such as promoters and enhancers act as “wires” to connect genes into regulatory networks and control nearby gene expression. Changes to regulatory networks are recognized as an important mechanism for organismal evolution (5), but mechanisms driving the emergence of new regulatory elements are still poorly understood. Owing to their ability to replicate throughout the host genome, TEs have long been hypothesized to play a role in the evolution of regulatory networks (6, 7). Although most TEs no longer encode functional proteins, many retain transcription factor binding sites and can thus alter the expression of nearby genes. Over the past decade, there have been numerous studies characterizing important roles for TEs in host gene regulation (reviewed in ref. 2). These findings point to the cooption of TEs as a general mechanism shaping the evolution of mammalian gene regulatory networks. As studies in … [↵][1]1To whom correspondence may be addressed. Email: edward.chuong{at}colorado.edu. [1]: #xref-corresp-1-1